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    DRUG:

    APTO-253

    i
    Other names: APTO-253, APTO 253, LOR-253, LT-253
    Associations

    News

    Trials
    Company:
    Aptose Biosci
    Drug class:
    Apoptosis stimulant, MYC inhibitor, KLF-4 stimulant, MTF-1 inhibitor
    Related drugs:
    Associations

    News

    Trials
    1year
    Suppression of super-enhancer-driven TAL1 expression by KLF4 in T-cell acute lymphoblastic leukemia. (PubMed, Oncogene)
    In addition, we found that APTO-253, a small molecule inducer of KLF4, exerts an anti-leukemic effect by targeting SE-driven TAL1 expression in T-ALL cells. Taken together, our results suggest that the induction of KLF4 is a promising strategy to control TAL1 expression and could be a novel treatment for T-ALL patients with a poor prognosis.
    Journal
    |
    MYB (MYB Proto-Oncogene, Transcription Factor) • KLF4 (Kruppel-like factor 4) • TAL1 (TAL BHLH Transcription Factor 1)
    |
    APTO-253
    1year
    Suppression of Super-Enhancer-Driven TAL1 Expression By KLF4 in T-Cell Acute Lymphoblastic Leukemia (ASH 2023)
    Finally, we investigated whether pharmacological induction of KLF4 using APTO-253, a small-molecule inducer of KLF4, could control leukemia...Moreover, pharmacological induction of KLF4 demonstrated anti-leukemic activity in T-ALL cells. These findings propose a promising strategy for patients with T-ALL and 5' TAL1 SE.
    IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • MYB (MYB Proto-Oncogene, Transcription Factor) • KLF4 (Kruppel-like factor 4) • TAL1 (TAL BHLH Transcription Factor 1)
    |
    KLF4 overexpression
    |
    APTO-253
    over1year
    Cuproptosis-Related Genes MTF1 and LIPT1 as Novel Prognostic Biomarker in Acute Myeloid Leukemia. (PubMed, Biochem Genet)
    In addition, APTO-253 has the potential to become an AML-targeted drug. The cuproptosis-related genes MTF1 and LIPT1 can be used as prognostic biomarkers in AML. A total of six lncRNAs, including MALAT1, are involved in the expression and regulation of MTF1 in AML through six miRNAs such as hsa-miR-32-5p.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MALAT1 (Metastasis associated lung adenocarcinoma transcript 1) • DLAT (Dihydrolipoamide S-Acetyltransferase) • MELTF (Melanotransferrin) • FDX1 (Ferredoxin 1) • LIAS (Lipoic Acid Synthetase) • LIPT1 (Lipoyltransferase 1) • MTF1 (Metal Regulatory Transcription Factor 1) • PDHA1 (Pyruvate Dehydrogenase E1 Subunit Alpha 1) • SLC31A1 (Solute Carrier Family 31 Member 1)
    |
    NPM1 mutation • MFI2 expression
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    APTO-253
    over1year
    KLF4-mediated upregulation of the NKG2D ligand MICA in acute myeloid leukemia: a novel therapeutic target identified by enChIP. (PubMed, Cell Commun Signal)
    These data unravel a novel link between APTO253 and the innate anti-tumor immune response providing a rationale for targeting AML cells via APTO253-dependent KFL4/MICA induction to allow elimination by endogenous or transplanted NK and T cells in vivo. Video Abstract.
    Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • KLF4 (Kruppel-like factor 4) • MICA (MHC Class I Polypeptide-Related Sequence A) • NKG2D (killer cell lectin like receptor K1)
    |
    MYC expression
    |
    APTO-253
    3years
    A Phase 1a/b Dose Escalation Study of the MYC Repressor Apto-253 in Patients with Relapsed or Refractory AML or High-Risk MDS (ASH 2021)
    APTO-253 has been well-tolerated at doses of 20, 40, 66, 100 and 150 mg/m 2 over multiple cycles and escalated to 210 mg/m 2 (Cohort 6). PK analysis revealed that APTO-253 is rapidly transformed to and co-exists with the Fe(253) 3 in serum from R/R AML and high-risk MDS patients. Enrollment of patients at the 210 mg/m 2 dose level is ongoing and updated clinical data will be presented at the meeting.
    Clinical • P1 data
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog)
    |
    MYC expression
    |
    APTO-253
    over3years
    [VIRTUAL] A PHASE 1A/B DOSE ESCALATION STUDY OF THE MYC REPRESSOR APTO-253 IN PATIENTS WITH RELAPSED OR REFRACTORY AML OR HIGH-RISK MDS (EHA 2021)
    PK analysis revealed that APTO-253 is rapidly transformed to and co-exists with the Fe(253)3 in serum and their exposures resulted in suppression of MYC expression in whole blood samples from R/R AML and high-risk MDS patients. Enrollment of patients at the 150 mg/m2 dose level is ongoing and updated clinical data will be presented at the meeting.
    Clinical • P1 data
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog)
    |
    MYC expression
    |
    APTO-253
    over3years
    Krüppel-Like Factor 4 and Its Activator APTO-253 Induce NOXA-Mediated, p53-Independent Apoptosis in Triple-Negative Breast Cancer Cells. (PubMed, Genes (Basel))
    Furthermore, treatment of TNBC cells with a KLF4-inducing small compound, APTO-253, resulted in the induction of NOXA expression and NOXA-mediated apoptosis. Therefore, our results help to clarify the molecular mechanism of DNA damage-induced apoptosis and provide support for a possible treatment method for p53-mutated cancers.
    Journal • IO biomarker
    |
    TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • KLF4 (Kruppel-like factor 4) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1)
    |
    TP53 mutation
    |
    APTO-253
    over3years
    MYC as a target for cancer treatment. (PubMed, Cancer Treat Rev)
    Based on its broad efficacy and limited toxicity, OmoMYC is currently being developed for evaluation in clinical trials. Although no compound directly targeting MYC has yet progressed to clinical testing, APTO-253, which partly acts by decreasing expression of MYC, is currently undergoing a phase I clinical trial in patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome.
    Review • Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
    |
    MYC overexpression • MYC expression
    |
    APTO-253
    4years
    [VIRTUAL] A Phase 1a/b Dose Escalation Study of the MYC Repressor Apto-253 in Patients with Relapsed or Refractory AML or High-Risk MDS (ASH 2020)
    APTO-253 has been well-tolerated in patients treated with 20, 40, 66, and 100 mg/m2 over multiple cycles. PK analysis revealed APTO-253 monomer rapidly transformed to and co-existed with the Fe(253)3 complex in peripheral blood and their exposures resulted in suppression of MYC expression in whole blood samples from R/R AML and high-risk MDS patients. Enrollment of patients at the 150 mg/m2 dose level is underway and updated clinical data will be presented at the meeting.
    Clinical • P1 data
    |
    FLT3 (Fms-related tyrosine kinase 3) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)
    |
    MYC expression
    |
    APTO-253